Fatal hepatocerebral syndrome in siblings discordant for exposure to valproate

Occurrence of a progressive encephalopathy with seizures in siblings was associated with hepatic pathology. One of these patients was exposed to valproate (VPA) and developed hepatic necrosis, confirmed at autopsy. The other had not been exposed to VPA, and her hepatic lesions at autopsy were less severe. The liver pathology in both was within the range described in previous cases of liver disease attributed to VPA. These facts and the otherwise similar course of their disease suggests that in these patients, and probably in other cases of fatal liver failure attributed to VPA, the drug actually either had no effect or acted only to increase the severity of the preexisting hepatic component of the hepatocerebral disorder.